TY - JOUR
AU - Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration
AU - Wang, Jun
AU - Kotagiri, Prasanti
AU - Lyons, Paul A.
AU - Al-Lamki, Rafia
AU - Mescia, Federica
AU - Bergamaschi, Laura
AU - Turner, Lorinda
AU - Morgan, Michael D.
AU - Calero-Nieto, Fernando J.
AU - Bach, Karsten
AU - Mende, Nicole
AU - Wilson, Nicola K.
AU - Watts, Emily R.
AU - Maxwell, Patrick H.
AU - Chinnery, Patrick F.
AU - Kingston, Nathalie
AU - Papadia, Sofia
AU - Stirrups, Kathleen E.
AU - Walker, Neil
AU - Gupta, Ravindra K.
AU - Menon, David K.
AU - Allinson, Kieren
AU - Aitken, Sarah J.
AU - Toshner, Mark
AU - Weekes, Michael P.
AU - Nathan, James A.
AU - Walmsley, Sarah R.
AU - Ouwehand, Willem H.
AU - Kasanicki, Mary
AU - Göttgens, Berthold
AU - Marioni, John C.
AU - Smith, Kenneth G.C.
AU - Pober, Jordan S.
AU - Bradley, John R.
PY - 2022
DA - February
TI - Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19
JO - iScience
VL - 25
IS - 3
DO - https://doi.org/10.1016/j.isci.2022.103971
AB - Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Factor Va (FVa). Using whole blood RNAseq and scRNAseq of peripheral blood mononuclear cells, we find that FV mRNA is expressed in leukocytes, and identify neutrophils, monocytes, and T regulatory cells as sources of increased FV in hospitalized patients with COVID-19. Proteomic analysis confirms increased FV in circulating neutrophils in severe COVID-19, and immunofluorescence microscopy identifies FV in lung-infiltrating leukocytes in COVID-19 lung disease. Increased leukocyte FV expression in severe disease correlates with T-cell lymphopenia. Both plasma-derived and a cleavage resistant recombinant FV, but not thrombin cleaved FVa, suppress T-cell proliferationin vitro. Anticoagulants that reduce FV conversion to FVa, including heparin, may have the unintended consequence of suppressing the adaptive immune system.
PB - Elsevier
UR - https://hdl.handle.net/2164/20034
KW - Coronavirus (COVID-19)
ER